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Chapter 9: Persistent Depressive Disorder (PPD) Daniel N. Klein Sarah R. Black Background Depressive disorders traditionally conceptualized as episodic, remitting conditions Shift to viewing depression as recurrent and chronic Reality is variability in course (e.g., single episode, recurrent episodes with full remission in between, chronic depression) Chronic depressions ~30% of cases in community and ~50% in outpatient settings Evidence that chronicity is a key aspect of the clinical and etiological heterogeneity of depression that should be considered in both clinical practice and research Description and Diagnostic Criteria DSM-5 Criteria: Dysthymic Disorder Chronic course, persistent symptoms, insidious onset At least two of six depressive symptoms required: Low energy or fatigue, insomnia or hypersomnia, poor appetite or overeating, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness Cognitive, affective, social-motivational symptoms more common than vegetative symptoms At some point, most individuals experience superimposed MDEs (“double depression”) With DSM-IV, given given both MDD and dysthymia diagnoses if experience double depression Persistent Depressive Disorder (PDD) Chronic course: most of day, more days than not, for at least two years Persistent symptoms: no symptom-free periods of more than 2 months Insidious onset typical: but ok if MDD present during first 2 years At least 2 of 6 depressive symptoms required: Low energy or fatigue, insomnia or hypersomnia, poor appetite or overeating, low self-esteem, poor concentration or difficulty making decisions, and feelings of hopelessness Cognitive, affective, social-motivational symptoms more common in PDD than are vegetative symptoms At some point, most individuals experience superimposed MDEs ( called “double depression” in the past) In DSM-5, those who would meet for DSM-IV chronic MDD will now receive PDD diagnosis Summary of DSM-5 Changes for Depressive Disorders Persistent Depressive Disorder – consolidation of DSM- IV criteria for chronic MDD & dysthymic disorder Same as criteria for dysthymia in DSM-IV, except D criteria DSM-IV: No MDE has been present during first 2 years of the disturbance DSM-5: Criteria for a MDD may be continuously present for first 2 years DSM-5 Persistent Depressive Disorder: Specifiers Partial remission versus full remission Early Onset (before 21) versus Late With pure dysthymic syndrome (no MDD in last 2 years) With persistent MDD (MDD met continuously in last 2 years- used to be called chronic depression) MILD: just meeting criteria and impairment is minor MODERATE: between mild and severe SEVERE: many criteria met, marked impairment and serious distress Chronic Versus Nonchronic Depressions Support for dysthymia versus MDD distinction: Milder symptoms, but dysthymia more severe on almost all other variables (e.g., greater suicidality and comorbidity, lower selfesteem) Validity of chronic–nonchronic MDD distinction less clear: However, some meaningful differences (e.g., chronic has earlier onset, poorer work and social functioning) Support for broader chronic-nonchronic distinction: Meaningful differences (e.g., chronic associated with greater childhood adversity, earlier age of onset) Chronic depression aggregates specifically in families Distinction relatively stable over time Forms of Chronic Depression Virtually no differences found between different forms of chronic depression (on variables like: comorbidity, personality, familial psychopathology, course, outcome) Thus, distinctions among various forms of chronic depression do not appear to be meaningful, in contrast to chronic– nonchronic distinction Decision made to combine different forms of chronic depression into single category in DSM-IV Dysthymia versus Depressive Personality Disorder Equivalent constructs in DSM-III Depressive PD was a provisional diagnosis in need of further study of DSM-IV; it was defined in terms of traits (mostly cognitive) and did not require persistent depressed mood Decision made not to include it in DSM-5 though it does appear to lie within the spectrum of chronic epressive disorders and does not require persistent depressed mood Subtypes of Dysthymia Several distinct etiological pathways Early (< 21) & late (≥ 21) onset specifiers in DSM-IV Early: Higher familial loading, childhood adversity, and so on Late: Greater association with stressful life events Subtypes within early-onset proposed: Subaffective vs. character spectrum Strong familial liability vs. early adversity and increased sensitivity of behavioral and neurobiological stress response systems DSM-5 Changes Now “Persistent Depressive Disorder”: Consolidation of DSM-IV criteria for chronic MDD and dysthymic disorder Same as criteria for dysthymia in DSM-IV, except D criteria DSM-IV: “No MDE has been present during first 2 years of the disturbance” DSM-5: “Criteria for a MDD may be continuously present for 2 years” Epidemiology Prevalence and Comorbidity Dysthymia: 12 months 0.5%-2.5%; lifetime 0.9%-6.4% Chronic MDD: 12 months 1.5%; lifetime, 3.1% Chronic depression combined: Lifetime 4.6% Prevalence of dysthymia and chronic MDD almost 2x greater in women than men Higher in developed countries and among individuals with lower incomes High comorbidity with anxiety, substance use, and personality disorders (especially avoidant, borderline, dependent PDs) Impairment Severity and chronicity contribute additively to functional impairment in depression Thus, dysthymia associated with equal or greater impairment than nonchronic MDD Double depression greater impairment than either alone Impairment in many areas (e.g., work functioning and marital, family, and social relationships) Significant impairment seen even after recovery Course and Prognosis Course and Prognosis In a 10-year follow-up study of dysthymia and double depression… 74% recovery rate 52 month median time to recovery 71% relapsed after recovery 6% developed manic or hypomanic episodes 84% superimposed MDEs Predictors of greater depressive symptoms at 10 years: Greater familial loading, history of poor maternal relationship, childhood sexual abuse Comorbid PD predicted slower rate of improvement Chronic Depression in Youth and Elderly Dysthymia in Children and Adolescents DSM-5: Minimum 1-year duration (versus 2 for adults); can have irritable instead of depressed mood Children: 0.1% point prevalence Adolescents: 0.5% prevalence; 3% lifetime High comorbidity with anxiety and disruptive behavior disorders Course Most eventually have superimposed MDEs Almost all eventually recover; median episode duration 4 years Greater risk of developing bipolar Dysthymia and Older Adults (> 65) Prevalence: 2%–6% Most late-onset (> 21) Compared to nonelderly with dysthymia: Lower rates of Axis I and II comorbidity, higher rates of recent life events, more GMCs Recovery rate: 12%–38% (15 months—6 years) Predictors of poorer course: Greater symptom severity, social isolation and low social support, poor self-reported health Psychosocial Factors Early Maltreatment and Adversity Predict poorer course and outcome Link between adversity and chronic depression could be explained by: Comorbidity with other mental disorders; however, relationship remains after controlling for other disorders Third variable (e.g., genes related to both) Future directions: Establish causal relationship Etiological pathways (e.g., development of depressogenic cognitive schemas) Most maltreated children do not later develop chronic depression; need to look for moderators of association Personality/Temperament and Chronic Stress Low positive emotionality (PE) and high negative emotionality (NE) predict poorer course and outcome in chronic depression Also may predict development of chronic depression Higher NE and lower PE in chronic than nonchronic depression and this personality seen after recovery as well as prior to illness Higher levels of chronic stress & daily hassles in chronic than nonchronic depression Chronic stress appears to play causal role in onset or maintenance of chronic depression (not reverse) Reduction or neutralization of ongoing difficulties and “freshstart” events associated with recovery Cognitive and Interpersonal Factors Similar cognitive factors seen as in nonchronic depression (e.g., stable and global attributions for negative events, ruminative response style) Directionality of relationship between maladaptive cognitive processes and depression unclear Interpersonal difficulties maintain and prolong depressive episodes Self-propagating processes proposed to maintain depression (e.g., negative feedback-seeking, excessive reassurance-seeking) Predict development of chronic depression • Greater difficulties after recovery than nonchronic MDD and HCs • Directionality unclear Genetic and Neurobiological Factors Familial Aggregation/Genetics Evidence of specificity of familial transmission in chronic depression Also higher rates of nonchronic MDD in relatives of probands with chronic than nonchronic depression Several findings suggest chronic depression characterized by a specific set of interacting genetic and environmental processes Childhood maltreatment moderates association between 5-HTTLR and chronic depression Neurobiology In major mood disorders, evidence of neuroendocrinology, sleep electrophysiology, and structural and functional brain abnormalities In chronic depression: Similar HPA axis abnormalities Inconsistent findings for sleep electrophysiology abnormalities Similar structural and functional abnormalities Too few studies to determine whether differences between chronic and nonchronic depression (e.g., whether any abnormalities are greater in or specific to chronic depression) Assessment Assessment: Overview Challenging task! Usually psychological assessments focus on acute conditions Dysphoria is “normal” for these individuals, often seek treatment for superimposed MDE Requires careful history of current and past course of depression Assessment: Tools Structured diagnostic interviews (e.g., SCID): Generally only assess for current dysthymia Limited information on onset, course, interepisode symptomatology Often miss double depression Rating scales (e.g., HAM-D) and self-reports: Course not adequately assessed to diagnose chronic depression Do not include the most common symptoms of dysthymia Refer to differences from “normal” or “usual” state Cornell Dysthymia Rating Scale addresses these problems General Behavior Inventory (GBI) is the only self-report measure explicitly developed for chronic mood disorders Treatment Treatment: Overview Pharmacotherapy All antidepressants equally more efficacious than placebo Lower placebo response in chronic than nonchronic MDD Antidepressants alone appear more efficacious than psychotherapy alone Indirect evidence that different approaches required Longer duration of psychotherapy More likely to benefit from combined meds and therapy Few predictors of differential response (to different meds or pharmacotherapy vs. psychotherapy) CBASP higher remission for chronically depressed with childhood adversity, whereas meds superior for individuals without childhood adversity Treatment preference impacts outcomes Treatment: Psychotherapy More efficacious than control conditions, but small effect size Minimum 18 sessions for optimal effects Cognitive behavioral analysis system of psychotherapy (CBASP) Specifically designed for chronic depression Uses behavioral and cognitive techniques to help patients develop better interpersonal problem-solving skills Interpersonal therapy (IPT) Psychodynamically inspired therapy that focuses on current interpersonal problems One of few comparisons of CBASP and IPT found higher remission rate for CBASP at post, but similar effects at 1-year follow-up Treatment: Nonresponse, Continuation and Maintenance Nonresponse and partial remission to initial trial of treatment high among chronically depressed Can change medications or Switch to/add psychotherapy or pharmacotherapy Continuation and maintenance treatment Important consideration due to high risk of relapse and recurrence Antidepressants lower risk of relapse and recurrence compared to placebo Some evidence psychotherapy effective as maintenance treatment Summary and Future Directions Summary The various forms of chronic depression appear to be more alike than different, and may represent variants or different phases of the same underlying disorder Chronic–nonchronic distinction appears to be meaningful Still, some heterogeneity within chronic depression Age of onset Episodes can last for many years, but most patients eventually recover Risk of recurrence high Predictors of poorer course and outcome: Family history, childhood adversity, comorbid anxiety and PDs, chronic stress Summary Treatment challenges: Entrenched psychopathology, comorbidity, longstanding interpersonal deficits, chronic helplessness and hopelessness, depression becoming integrated into individual’s self-image and daily routine Antidepressants and some psychotherapies (e.g., CBASP) found effective, and combination may be more effective Maintenance treatment can prevent recurrences Future Directions Genetically informative studies (e.g., genome-wide association studies, gene-by-environment interactions) Causal processes producing high psychiatric comorbidity Etiological pathways Protective factors, environmental variables that facilitate recovery (e.g., “fresh-start” events) Developing tools that better assess course Psychotherapy: Identifying active ingredients, optimal parameters, specificity and range of effective treatments Improve remission rates from meds and therapy How to sequence and combine treatments to optimize outcomes